#ESMO26 DASL-HiCaP Presidential Discussant -- @Silke_Gillessen Differences in BL risk and pt selection may explain variation in treatment effects for STAMPEDE M0, ENZARAD, DASL-HiCaP Among N1 pts only, ARPI MFS benefit: ◾️STAMPEDE M0: HR 0.49, 95%CI 0.38-0.64 ◾️ENZARAD: HR 0.43, 95%CI 0.20-0.92 ◾️DASL-HiCaP: HR 0.39, 95%CI 0.19-0.81

Putting STAMPEDE, ENZARAD, PROTEUS & DASL into context with the latest #ESMO26 updates: STAMPEDE: Abiraterone-based intensification improved MFS AND OS, predominantly with RT. New #ESMO26 Decipher data suggests differential abi benefit in cN0 disease (interaction P=.01); using this to omit treatment still requires validation. ENZARAD: At 8 years, MFS was 74% vs 72% (HR 0.88; P=.34). No significant overall MFS benefit from enza + ADT/RT. The cN1/planned pelvic RT subgroup signals remain hypothesis-generating. DASL: new at #ESMO26: 1,106 patients; 96 weeks of daro v. placebo + ADT + prostate/bed AND pelvic RT. Four-year conventional-imaging MFS: 95% vs 88% (HR 0.42). Very-high-risk population, including selected postoperative patients. Interim analysis; OS immature. PROTEUS main trial: Perioperative apa + ADT improved 5-year PSMA-inclusive MFS versus ADT alone: 78.2% vs 73.5% (HR 0.80). Conventional-imaging MFS was not statistically significant. #ESMO26 post hoc PSA-response analysis adds prognostic information. PROTEUS randomized substudy: new at #ESMO26: Perioperative apa/ADT + RP/PLND (n=102) v. immediate RP/PLND (n=306). At 37.8 months’ follow-up: • 3-year EFS: 63.0% vs 41.4%; HR 0.38. • Secondary PSMA-inclusive MFS: HR 0.49; nominal P=.0193. • Subsequent postoperative RT: 20% vs 43%. The substudy strengthens a "perioperative strategy". But conventional-imaging entry followed by PSMA-inclusive endpoints matters. PSA-based EFS, conventional MFS and PSMA-inclusive MFS are different endpoints. These trials support specific intensification strategies; they cannot rank the drugs or establish RP-versus-RT superiority. The decision remains who benefits enough to justify the ENTIRE treatment burden.

New findings from the randomized Phase III STAMPEDE trial took the stage at #ESMO26 today. Here’s a recap from a session where Sarah Howlett, M.B.B.S., University College London (@ucl), presented results from a combination analysis of STAMPEDE and real-world datasets. The talk highlighted how the Decipher® Prostate Genomic Classifier can predict benefit from adding abiraterone to androgen deprivation therapy (ADT) in men with clinically very high-risk #ProstateCancer, whose disease had not spread to lymph nodes. | Primary Takeaways | 🔹 Transcriptomic signatures showed consistent associations with metastatic outcomes across both STAMPEDE and real-world datasets. 🔹 Higher Decipher scores identified patients with higher rates of distant metastasis and those most likely to benefit from the addition of abiraterone. 🔹 Lower Decipher scores correlated with lower rates of distant metastasis, potentially providing means for guiding safe treatment de-escalation. | Some Thank You’s | 💙 We’re grateful to Dr. Howlett for sharing this research with the oncology community and for her continued dedication to improving care for the millions of men living with prostate cancer worldwide. 💙 Thank you to everyone who joined the session and to the investigators, site teams, and participants whose contributions made this research possible. | Additional Resources | 🔗 Event information - veracyte.com/company/event/e… 🔗 Decipher Prostate Genomic Classifier - veracyte.com/tests/decipher-… #PrecisionOncology #ClinicalResearch #RealWorldData #DecipherProstate #TeamVeracyte Note: This article contains forward-looking statements, which involve risks and uncertainties. For more info visit - veracyte.com/legal/cautionar…

We are proud to announce new Phase III study findings showing that the Decipher® Prostate Genomic Classifier can predict benefit from adding abiraterone to androgen deprivation therapy (ADT) in men with clinically very high-risk #ProstateCancer. This retrospective analysis of the randomized Phase III STAMPEDE trial provides new Level 1B predictive evidence for Decipher Prostate test in patients with clinically high-risk nonmetastatic prostate cancer whose disease had not spread to lymph nodes. | Key Findings | 🔹 Decipher predicted benefit from adding abiraterone: The treatment-by-Decipher interaction for distant metastasis was statistically significant among node-negative patients (p=0.01), indicating that treatment benefit differed according to the Decipher score. 🔹 Patients with higher Decipher scores saw greater benefit: At five years, the benefit for adding abiraterone in terms of reducing distant metastasis events was 10% for patients with high scores and 11% for those with very high scores, compared to 2% benefit for those with lower scores. 🔹 Decipher scores helped identify differences in the risk of cancer spread: Higher scores were associated with greater distant-metastasis risk and worse metastasis-free and overall survival in the STAMPEDE cohort. These findings build on Decipher’s established ability to help assess the risk of cancer progression, expanding the test’s predictive evidence to another consequential treatment decision. Dr. Sarah Howlett, M. B.B. S. of University College London will present the completed results in a proffered paper oral presentation at the #ESMO26 Congress (Abstract 2045O). | Presentation Details | 📌 Title: Transcriptome classifier risk stratification and intensification with androgen receptor pathways inhibitors (ARPI) for clinically high-risk prostate cancer 📅 Date: Saturday, October 24 ⏰ Time: 10:15 a.m. – 11:45 a.m. CEST 📍 Location: Barcelona Auditorium – Hall 9 | Resources| 📄  Read full press release - investor.veracyte.com/news-r… 🔗 Event information - veracyte.com/company/event/e… #PrecisionOncology #ClinicalResearch #DecipherProstate #TeamVeracyte This article contains forward-looking statements. These forward-looking statements involve risks and uncertainties. Please visit our website for more information: veracyte.com/legal/cautionar…

Nice one @ucl @AttardLab independent.co.uk/news/uk/ho…

🚨 Focal salvage HDR brachy for radiorecurrent #prostatecancer🚨 📜@JCO_ASCO 👥 n=62, intraprostatic radiorecurrence after prior RT, multi-institutional 📊 Phase 1/2, dose-escalated focal salvage HDR, up to 30 Gy in 1 to 2 fractions ⏱️ Median f/u 39.4 mo ✅ No acute grade 3 toxicity; late grade 3 in 2 pts (3.2%) ✅ 3-yr bPFS 62.7%, MFS 85.9% ✅ Higher Decipher GC score tracked w/ worse bPFS, rPFS, MFS; all 4 pts w/ GC >0.85 recurred ⚠️ Small GC subset (n=31), single-arm, hypothesis-generating 🎯 Focal salvage HDR is well tolerated & a genomic classifier may prognosticate 🔗 doi.org/10.1200/JCO-25-02730 @UroOnc @urotoday @UrologyTimes @PCF_Science @Davicioni

🔬 Can genomic classifiers help us personalise salvage treatment for recurrent prostate cancer after radiotherapy? ascopubs.org/doi/10.1200/JCO… Dose-Escalated Focal Salvage High-Dose-Rate Brachytherapy and Genomic Classifier Risk Stratification in Radiorecurrent Prostate Cancer: The F-SHARP Phase I/II Clinical Trial The F-SHARP phase I/II trial evaluated dose-escalated focal salvage high-dose-rate brachytherapy (DE-fsHDR) for intraprostatic radiorecurrence following prostate radiotherapy☢️ ➡️Among 62 patients, treatment demonstrated a favourable safety profile, with no acute grade 3 toxicities and 3.2% late grade 3 toxicity. ✅Three-year metastasis-free survival reached 85.9%. Higher genomic classifier scores correlated with poorer outcomes, highlighting their potential to identify patients who may benefit from treatment intensification. Further validation is needed. #ProstateCancer @abhiasolanki @ndesai2005 @DrMikeFolkert @gupta_go @TimShowalter1 @SteveKregel @MattHarkenrider @Davicioni @OncoAlert 🚨 #LPCCC27 @Silke_Gillessen @AOmlin @ProfKHerrmann @weoncologists

1/6: I am excited to share our multi-institutional F-SHARP phase I/II trial, now published in @JCO_ASCO! doi.org/10.1200/JCO-25-02730 There are limited prospective data defining the optimal management of intraprostatic radiorecurrence (IPR) after definitive RT for prostate cancer. We asked: 1. Is dose-escalated focal salvage high dose rate brachytherapy safe and effective for IPR? 2. Can Decipher (@Veracyte) identify patients with higher risk of recurrence with salvage ReRT that may benefit from therapeutic intensification? 🧵👇

4/6 | Decipher This is the first prospective evaluation of the prognostic impact of Decipher in the setting of IPR. 71% had high genomic risk (>0.60), a proportion higher than in the de novo setting. Decipher scores from IPR biopsies were prognostic across biochemical, radiographic, local, and metastatic outcomes. Suggesting it may identify patients who may benefit from local and systemic treatment intensification.

Genomic stratification of benefit from short-term androgen deprivation with dose-escalated radiotherapy in intermediate-risk #ProstateCancer: an ancillary study of NRG/ROTG 0815. Presentation by @angela_jia_ @RadOncUH. #ASTRO26 written coverage by @zklaassen_md > bit.ly/4z7EjC3 @ASTRO_org

This is the struggle. The clearest guidance comes when a biomarker is both prognostic of worse outcomes and predictive of benefit from an intervention that improves those outcomes. Luminal B illustrates this: the RTOG 0534 analysis supports greater benefit from short-term ADT, while NRG-GU006 demonstrated benefit from adding apalutamide to salvage RT in this subtype. The harder scenario is when the prognostic and predictive signals diverge—for example, a non–luminal B tumor with a high Decipher score. The prognostic signal pushes us toward intensification, but the subtype-specific evidence for hormonal benefit is less convincing. Do we add treatment because the risk is higher, even when the evidence that this particular intervention will reduce that risk is uncertain? Knowing who is more likely to recur is not the same as knowing which treatment will prevent that recurrence.

Association of 22-gene genomic classifier with ADT use with secondary radiotherapy: A national real-world analysis. Presentation by Andrew Barsky, MD @PennMedicine. #ASTRO26 written coverage by @RKSayyid @UAUrology > bit.ly/4hm59k3 @ASTRO_org

Had a wonderful time discussing the role of biomarkers in prostate cancer along side some amazing friends and fellow panelists! @mouwlab @ChadTangMD @DrSpratticus @ASTRO_org @ClevelandClinic @DrJohnSuh

🚨Decipher score predictive of ADT benefit for preventing metastasis in patients with intermediate-risk #ProstateCancer in secondary analysis of @NRGonc RTOG 0815 RCT @angela_jia_ @ASTRO_org #ASTRO26

#ASTRO26 @angela_jia_ and team bringing the 🔥 with incredibly important data. Translational study of @NRGonc RTOG 0815 showing Decipher was prognostic and predictive and those with lower decipher do benefit from ADT with RT. #pcsm @TylerSbrt @urotoday @DrChoueiri @AmarUKishan @DrHowardSandler @MutlaySayan @jmmrad @ASTRO_org @NehaVapiwala

New #ASTRO2026 data from @NRGOnc /RTOG 0534 SPPORT 🔬🧬 presented by Shuang (George) Zhao @UTMDAnderson. PAM50 Luminal B = both prognostic & predictive of benefit from postop ADT. 📈 5-y FFP benefit: 31% vs 10% (p-int=.01) 🎯 10-y MFS: 20% vs -3% (p-int=.05) #Pcsm @Astro_org

Could molecular subtype tell us who actually needs treatment intensification after prostatectomy? 🧬 Link to Abstract PRESENTED AT #ASTRO26 amportal.astro.org/sessions/… EVALUATION OF PAM50 MOLECULAR SUBTYPES IN POST-PROSTATECTOMY SALVAGE RADIOTHERAPY ☢️ : AN NRG ONCOLOGY-RTOG 0534 ANALYSIS In the randomized phase 3 NRG/RTOG 0534 SPPORT trial, PAM50 LumB prostate cancer identified men who derived substantially greater benefit from postoperative treatment intensification. ➡️ Among 709 profiled patients, adding short-term ADT ± pelvic nodal RT produced a 31% absolute 5-year FFP benefit in LumB versus 10% in non-LumB tumors, with significant treatment interactions. ➡️ LumB status was also associated with greater 10-year MFS benefit, supporting molecular subtyping to personalize salvage radiotherapy. @Davicioni, @a_dalpra, @ChrisMaher_Lab, @jmmrad, @DrPaulNguyen @OncoAlert 🚨 #LPCCC27 @Silke_Gillessen @AOmlin @ProfKHerrmann @weoncologists

5/5 We also evaluated transcriptomic signatures that may predict efficacy and toxicity following salvage HDR brachytherapy in F-SHARP. @LoyolaHealth @Davicioni

🚨 Genomic classifier scores are helping deciding who goes on active surveillance for #ProstateCancer🚨 @JNCI_Now, SEER linkage 2015-2018 👥 2,547 men w/ low or intermediate clinical risk PCa and a 22-gene GC score 📊 Population-based analysis, GC category vs initial management ✅ Immediate treatment vs AS/WW: OR 1.98 for intermediate GC, OR 4.42 for high GC (95% CI 3.41 to 5.71) ✅ Low clinical risk: 20.5% treated w/ low GC vs 46.2% w/ high GC ✅ Intermediate clinical risk: 57.5% vs 88.3% ⚠️ We still do not know whether GC predicts long-term outcomes for men managed w/ AS 🎯 Molecular markers are moving real treatment decisions at population scale. Can't tell if this is precision medicine or premature extrapolation! 🔗 doi.org/10.1093/jnci/djag247 @AmerUrological @UroOnc @SUO_YUO @PCFnews @mleapman @Davicioni @TylerSbrt @PCF_Science @Yale_Urology